Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut syndrome (LGS) is a rare, severe form of childhood epilepsy that is characterized by multiple types of seizures, slow spike-and-wave patterns on electroencephalography (EEG), and developmental delays/cognitive impairment. It is classified as a type of epileptic encephalopathy.¹

Individuals with LGS have an increased risk of mortality from related complications, including sudden unexpected death in epilepsy (SUDEP) and injuries sustained during seizure-related falls and accidents, particularly those involving the head and face.^2,3 Individuals with LGS have a 24-fold increased risk of premature death.¹ More common complications of LGS include mobility impairment, aspiration pneumonia, cognitive impairment, behavioral problems, sleep disturbances, and treatment resistance.

Sudden Unexpected Death in Epilepsy

Sudden unexpected death in epilepsy (SUDEP) is a major complication of LGS, with the highest risk being among patients who experience frequent convulsive seizures.² While the exact cause of SUDEP is unknown, researchers and clinicians speculate that it may be related to post-seizure heart and breathing issues.²

Read more about LGS life expectancy

Falls and Injuries During Seizures

Patients with LGS experience many types of seizures over the course of their condition, some of which carry an increased inherent risk of falls and injury. Atonic seizures result in a complete loss of muscle tone. If this occurs when the patient is standing or walking, abrupt falls increase the risk of injury, especially to the head and face.² Tonic seizures cause stiffening of the neck, arms, and legs. While they often occur during sleep, this doesn’t eliminate the danger to the sleeping person’s body. They may also occur during the day when the patient is upright, leading to a fall.²

While atonic and tonic seizures have higher risks of injury and falling, the altered awareness and confusion that occur during an atypical absence seizure, among other types, may also predispose patients with LGS to accidental injuries.²

Read more about LGS risk factors

Mobility Impairment

Balance impairment and lack of muscle coordination are the most common mobility impairments experienced by patients with LGS, increasing the risk of falling during locomotion. Another related complication of muscle coordination is dysphagia, which causes problems with feeding and swallowing.²

According to one study that retrospectively analyzed claims among patients with LGS, mobility restrictions may be severe in this patient population, with approximately one-third of patients having claims for wheelchair or walker use.⁴ 

Aspiration Pneumonia

Aspiration pneumonia may result from the unintentional inhalation of saliva during a seizure. It can also be linked to a patient’s decreased mobility and dysphagia.^2,5 Limited mobility is known to affect the strength and function of the respiratory muscles, which are required for airway clearance, increasing the risk of pneumonia.⁵ Dysphagia also increases the risk of aspiration of saliva or food due to problems coordinating the muscles involved in swallowing.^2,5

Onfi® (clobazam), an adjunctive therapy approved by the US Food and Drug Administration (FDA) to treat seizures in patients with LGS aged 2 years and older, has the side effects of hypersalivation, sedation, and behavioral changes in this patient population. These medication side effects increase the risk of developing aspiration pneumonia in those with LGS.⁶

Read more about LGS therapies

Cognitive Impairment 

Intellectual disabilities may or may not be apparent at disease onset and are not required for a patient’s initial diagnosis.^2,4

Cognitive impairments and learning disabilities often become severe by the time affected children reach adolescence. Achieving milestones and gaining developmental skills are delayed in many children with LGS.^2,4

Read more about LGS diagnosis

Behavioral Problems 

As children with LGS age, behavioral problems such as aggression, rage attacks, inattention, hyperactivity, and autism become more apparent.^2,4

Sleep Disturbances

Patients with LGS may experience difficulties falling or staying asleep. Because of the frequency of seizures, patients often wake during the night and get poor sleep.⁴ While some patients with LGS lead relatively normal lives, the LGS Foundation estimates that more than half of patients experience these aforementioned disease-related complications.⁴

Antiseizure Medication Resistance

Seizures experienced by patients with LGS are often refractory to available antiseizure treatments.^7,8 One source reports that more than 90% of children with LGS demonstrate drug-resistant epilepsy.⁷

Read more about LGS treatment

References

1. Lennox Gastaut syndrome. LGS Foundation. Accessed February 14, 2023.
2. Ajinkya S, Wirrell E. Lennox-Gastaut syndrome. Child Neurology Foundation. Accessed February 14, 2023.
3. Cherian KA. Lennox-Gastaut syndrome clinical presentation: complications. Medscape. Updated August 6, 2020. Accessed February 14, 2023. 
4. Reaven NL, Funk SE, Montouris GD, Saurer TB, Story TJ. Burden of illness in patients with possible Lennox–Gastaut syndrome: a retrospective claims-based study. Epilepsy Behav. 2018;88:66-73. doi:10.1016/j.yebeh.2018.08.032
5. Ajinkya S, Wirrell E. What is Lennox-Gastaut syndrome? LGS Foundation. Updated December 21, 2022. Accessed February 14, 2023.
6. Aung T, Shvarts V. Rare but life-threatening aspiration pneumonia related to initiation of clobazam therapy. Epilepsy Behav Rep. 2020;14:100406. doi:10.1016/j.ebr.2020.100406
7. Ostendorf AP, Ng YT. Treatment-resistant Lennox-Gastaut syndrome: therapeutic trends, challenges and future directions. Neuropsychiatr Dis Treat. 2017;13:1131-1140. doi:10.2147/NDT.S115996
8. VanStraten AF, Ng YT. Update on the management of Lennox-Gastaut syndrome. Pediatr Neurol. 2012;47(3):153-161. doi:10.1016/j.pediatrneurol.2012.05.001

Reviewed by Hasan Avcu, MD, on 2/21/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.